In a groundbreaking development, the FDA has granted approval for Merck’s Keytruda to be employed in a continuous immunotherapy regimen for resectable non-small cell lung cancer (NSCLC) patients, both before and after surgery. This decision marks a significant shift in the treatment landscape for NSCLC, offering newfound hope to patients.
Keytruda, a PD-1 inhibitor, has previously been used in either a neoadjuvant regimen prior to surgery or as an adjuvant therapy post-surgery. However, this approval extends its application to both stages of treatment, with patients concurrently receiving chemotherapy before surgical intervention.
The decision is a notable triumph for Merck, as their updated label includes data from the Keynote-671 study, revealing a remarkable 28% reduction in the risk of mortality when Keytruda was added to neoadjuvant chemo compared to chemo alone. Patients receiving neoadjuvant chemo alone had a median survival of 52.4 months, while those in the Keytruda arm displayed an unprecedented survival advantage with no reached median result at the time of the analysis, according to Monday’s FDA label update.
The revelation of overall survival data is a surprising turn of events, as it was anticipated to debut at the upcoming European Society for Medical Oncology 2023 Congress. This development is expected to significantly enhance Keytruda’s market prospects, despite it being one of the world’s top-selling therapies. Nevertheless, competition looms on the horizon, with positive results reported by Bristol Myers Squibb and AstraZeneca in the same perioperative setting.
Beyond the striking overall survival benefit, Keynote-671 demonstrates that the use of Keytruda in both neoadjuvant and adjuvant settings dramatically reduces the risk of tumor recurrence, progression, or death by an impressive 42% for patients with resectable stage 2 to 3b NSCLC.
Daina Graybosch, Ph.D., an analyst at Leerink Partners, previously lauded Keytruda’s event-free survival results as “impressive.” Nevertheless, it narrowly fell short of the 45% benchmark that clinicians had anticipated to indicate additional benefits from sustained adjuvant use of a PD-1 inhibitor in conjunction with neoadjuvant treatment.
Keytruda’s approval follows the green light granted to BMS’ Opdivo as a neoadjuvant therapy for stage 1b to 3a NSCLC last year. In the CheckMate-816 trial, Opdivo, when added to chemotherapy before surgery, achieved a 37% improvement in event-free survival (EFS) for patients in that category. Furthermore, recent data from the CheckMate-77T trial by BMS revealed significant EFS improvements when Opdivo was used both before and after surgery. Detailed data from CheckMate-77T is slated for presentation at ESMO.
A more extended follow-up of the CheckMate-816 trial, disclosed in March, demonstrated that neoadjuvant Opdivo led to a 38% reduction in the risk of death, although it had not yet reached statistical significance.
The distinction between Opdivo’s EFS improvements and Keytruda’s overall survival advantage will aid healthcare professionals in selecting the most suitable therapy and determining whether continued PD-1 treatment in the adjuvant setting is warranted after neoadjuvant therapy. Additionally, AstraZeneca has reported promising EFS data for perioperative Imfinzi in the phase 3 AEGEAN trial, though it is unlikely to prompt immediate regulatory action due to the relatively short follow-up period.
Meanwhile, the release of data from Roche’s IMpower-030 trial for perioperative Tecentriq has faced multiple delays and is now anticipated in 2024.
Notably, Keytruda has also obtained perioperative approval for the treatment of specific triple-negative breast cancer patients, expanding its reach even further. This FDA decision marks a significant stride forward in the quest for improved cancer treatment options, offering hope and potential new lease on life to countless patients.
